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Transplant immunology

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https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#1
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28936583/effective-immunological-guidance-of-genetic-analyses-including-exome-sequencing-in-patients-evaluated-for-hemophagocytic-lymphohistiocytosis
#2
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Christian Klemann, Sebastian F N Bode, Carsten Speckmann, Gritta Janka, Katharina Wustrau, Mirzokhid Rakhmanov, Ilka Fuchs, Hans C Hennies, Stephan Ehl
We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results...
September 21, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28935847/cd56bright-nk-regulatory-cells-in-filgrastim-primed-donor-blood-or-marrow-products-regulate-chronic-gvhd-cbmtg-randomized-0601-study-results
#3
Amina Kariminia, Sabine Ivison, Bernard Ng, Jacob Rozmus, Susanna Sung, Avani Varshney, Mahmoud Aljurf, Silvy Lachance, Irwin Walker, Cindy Toze, Jeff Lipton, Stephanie J Lee, Jeff Szer, Richard Doocey, Ian Lewis, Clayton Smith, Naeen Chaudhri, Megan K Levings, Raewyn Broady, Gerald Devins, David Szwajcer, Ronan Foley, Sara Mostafavi, Steven Pavletic, Donna A Wall, Stephen Couban, Tony Panzarella, Kirk R Schultz
Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease...
September 21, 2017: Haematologica
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#4
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28932650/gene-editing-gene-therapy-and-cell-xenotransplantation-cell-transplantation-across-species
#5
REVIEW
Nizar I Mourad, Pierre Gianello
PURPOSE OF REVIEW: Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation. RECENT FINDINGS: In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/28931653/combined-ox40l-and-mtor-blockade-controls-effector-t-cell-activation-while-preserving-treg-reconstitution-after-transplant
#6
Victor Tkachev, Scott N Furlan, Benjamin Watkins, Daniel J Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S Miller, Bruce R Blazar, Duncan Casson, Phil Bland-Ward, Leslie S Kean
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function...
September 20, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28930983/personalized-peptide-arrays-for-detection-of-hla-alloantibodies-in-organ-transplantation
#7
Pan Liu, Tomokazu Souma, Andrew Zu-Sern Wei, Xueying Xie, Xunrong Luo, Jing Jin
In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-HLA immunity, which presents either as pre-existing or de novo generated HLA antibodies that constitute a major transplantation barrier. Current tests are built on a single-antigen beads (SAB) platform using a fixed set of ~100 preselected recombinant HLA antigens to probe transplant sera...
September 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930796/navigating-t-cell-immunometabolism-in-transplantation
#8
Naoki Tanimine, Laurence A Turka, Bhavana Priyadharshini
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28930779/inhibition-of-lymphatic-drainage-with-a-self-designed-surgical-approach-prolongs-the-vascularized-skin-allograft-survival-in-rats
#9
Jiaomiao Pei, Yang Li, Chen Chen, Xi Zhang, Shiping Wang, Yajuan Song, Bei Liu, Yingjun Su, Shuzhong Guo
Vascularized composite allotransplantation (VCA) is an emerging treatment for significant tissue defects. However, VCAs usually consist of multiple highly antigenic skin tissues. Previous studies have shown that the lymphatic system in skin plays important roles in the initiation of immune responses during acute rejection, by transporting T cells and antigen-presenting dendritic cells to regional lymph nodes. Therefore, we designed a new surgical treatment to inhibit lymphatic drainage of skin allografts and investigated whether this approach could promote the survival of allografts and suppress immunological events after transplantation...
September 19, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28926127/recall-features-and-allorecognition-in-innate-immunity
#10
REVIEW
Hirofumi Uehara, Koichiro Minami, Markus Quante, Yeqi Nian, Timm Heinbokel, Haruhito Azuma, Abdala El Khal, Stefan G Tullius
Alloimmunity traditionally distinguishes short-lived, rapid and non-specific innate immune responses from adaptive immune responses that are characterized by a highly specific response initiated in a delayed fashion. Key players of innate immunity such as natural killer (NK) cells and macrophages present the first-line defense of immunity. The concept of unspecific responses in innate immunity has recently been challenged. The discovery of pattern recognition receptors (PRRs) has demonstrated that innate immune cells respond in a semi-specific fashion through the recognition of pathogen-associated molecular patterns (PAMPs) representing conserved molecular structures shared by large groups of microorganisms...
September 19, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28923650/does-renal-tubular-injury-induced-local-tissue-hypoxia-involve-post-transplantation-erythrocytosis
#11
A Unal, S Ata, C Karakurkcu, M Z Ciraci, I Kocyigit, M H Sipahioglu, B Tokgoz, O Oymak
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923633/changes-in-dna-methylation-of-glucocorticoid-induced-tumor-necrosis-factor-receptor-and-its-ligand-in-liver-transplantation
#12
W Wang, G Ji, Y Chen, J Wang, J Sun, G Tang, Z Xie, H Zhao, G Liu, S Tan, G Chen, H Xue
Liver transplantation (LT) is the criterion standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. Chronic immune rejection of the liver transplant can lead to bad prognosis for patients. Glucocorticoid-induced tumor necrosis factor receptor (GITR) play a key role in dominant immunologic self-tolerance maintained by CD25+/CD4+ regulatory T cells. Here, we investigated the DNA methylation variations of GITR and GITR ligand (GITRL) using pyrosequencing by analyzing blood DNA samples of patients after LT...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923614/flow-cytometry-panel-reactive-antibody-screening-of-anti-hla-antibodies-in-the-waiting-list-significantly-reduces-the-occurrence-of-acute-rejection-after-kidney-transplantation
#13
I Dedinská, N Mäčková, K Macháleková, J Miklušica, B Palkoci, J Fialová, M Čellár, P Galajda, M Mokáň
INTRODUCTION: The presence of preformed HLA-reactive antibodies in recipient serum before transplantation has long been recognized as a prominent risk factor for a generally worse graft outcome. Screening and identification of HLA antibodies can be used to stratify patients into high- and low-risk categories. MATERIALS AND METHODS: We determined patients' anti-HLA antibodies using flow cytometry panel-reactive antibody (flowPRA) screening, specifying more than 5% after positive screening...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28915342/transplantation-of-solid-organ-recipients-shedding-epstein-barr-virus-dna-pretransplant-a-prospective-study
#14
Priya S Verghese, David O Schmeling, Emma A Filtz, Jennifer M Grimm, Arthur J Matas, Henry H Balfour
Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival posttransplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease posttransplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years...
September 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28904948/recent-progress-in-deciphering-the-etiopathogenesis-of-primary-membranous-nephropathy
#15
REVIEW
Andreas Kronbichler, Jun Oh, Björn Meijers, Gert Mayer, Jae Il Shin
Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50-100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904861/a-modified-graft-versus-host-induced-model-for-systemic-sclerosis-with-pulmonary-fibrosis-in-rag2-deficient-mice
#16
Xue Yang, Chi Liu, Masayuki Fujino, Ji Yang, Xiao-Kang Li, Hejian Zou
Systemic sclerosis (SSc) is a connective tissue disease that results in fibrosis in multiple organs. Various animal models for this disease have been developed, both genetic and induced. One of the induced models, sclerodermatous graft-versus-host disease (scl-GvHD), exhibits the main characteristics of SSc, but involves lethal γ-irradiation of recipients. We sought to develop a modified scl-GvHD model. Spleen cells from B10.D2 donor mice were transplanted into immunodeficient Rag-2 recipients on the BALB/c genetic background...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28894451/inflammatory-conditions-dictate-the-effect-of-mesenchymal-stem-or-stromal-cells-on-b-cell-function
#17
Franka Luk, Laura Carreras-Planella, Sander S Korevaar, Samantha F H de Witte, Francesc E Borràs, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn, Marcella Franquesa
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28894081/eculizumab-in-renal-transplantation-a-2017-update
#18
Ryszard Grenda, Magdalena Durlik
Despite ongoing progress in renal transplantation, there are still emerging challenges in this field, including consequences of ischemia-reperfusion injury (IRI), pre-existing and produced de novo anti-HLA donor-specific antibodies (DSA), and acute/chronic humoral rejection (AMR), as well as the recurrence of atypical hemolytic-uremic syndrome (aHUS) in genetically predisposed patients. All these conditions are related to the prominent role of the complement system and are deleterious to the fate of the renal graft...
September 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28892571/regenerative-immunology-the-immunological-reaction-to-biomaterials
#19
Paolo Cravedi, Samira Farouk, Andrea Angeletti, Lauren Edgar, Riccardo Tamburrini, Jerome Dusuit, Laura Perin, Giuseppe Orlando
Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes...
September 11, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28891156/overcoming-pre-existing-alloantibody-in-renal-transplantation-improving-outcomes-while-reducing-need-and-cost
#20
EDITORIAL
A Bentall, Solomon Shlomo J Cohney
In this week's journal, Axelrod and colleagues examine costs incurred by various US centers undertaking Incompatible Live-Donor Kidney Transplantation (ILDKT) - living donor renal transplantation in the presence of preformed antibody (ies) directed against donor HLA (DSAb) [1]. As expected, cost increased as the immunological barrier intensified (as defined by solid phase and cell based assays). While certain aspects of cost recovery are specific to US health care, effectively managing humoral allo-immunity is important to all transplant clinicians, with little progress despite nearly 2 decades of ILDKT [2, 3]...
September 11, 2017: American Journal of Transplantation
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